The present invention relates to a novel salt of an organic pyrophosphoric acid compound. It also relates to an agent for treating lymphocytes containing the organic pyrophosphoric acid compound or the salt thereof which effectively induces and potentiates an antitumor effect, Vxcex32Vxcex42 type T cells treated by the agent for treating lymphocytes and to a medicine containing the same.
As a method for inducing and enhancing an antitumor effect in human lymphocytes, it has been known LAK therapy using interleukin-2. That is, it has been known that by having about 800 U/ml of interleukin-2 to act on the lymphocytes, cell groups induced thereby with an antitumor activity can be used as an antitumor effecter. However, in this method, there are serious side effects, for example, destruction of the self cells such as endovascular cells due to non-specific cytotoxic property possessed by LAK cells and the like or induction of autoimmunity due to non-specific activation of T cells by interleukin-2, thereby making it difficult to apply this methods to an actual clinical field.
As compounds which specifically activate Vxcex32Vxcex42 type T cells, there have been known mycobacteria-derived isopentenyl pyrophosphoric acid and mono ethyl phosphoric acid obtained by an organic synthesis. In those methods, however, the concentrations of those compounds are required to be several hundreds of xcexcM to several mM in order to activate Vxcex32Vxcex42 type T cells. Such high concentrations of the compounds may have a toxic effect on the cells, therefore, it was difficult to use those compounds to induce and enhance an antitumor effect of the lymphocytes in a large scale. In any case, it has not yet been known a synthetic compound which can act on the Vxcex32Vxcex42 type T cells in a concentration of several hundreds of nM to several hundreds of xcexcM, and specifically proliferate those cell groups.
The present invention has been aimed to solve the above-mentioned problems of the prior art. An object of the present invention is to provide a novel compound that can specifically stimulate and proliferate the human Vxcex32Vxcex42 type T cells, an agent for treating lymphocytes that induces and/or potentiates an antitumor effect of the human Vxcex32Vxcex42 type T cells, Vxcex32Vxcex42 type T cells treated by the same, and a medicine which comprises the same.
The present inventors have made extensive and intensive studies in search for a compound that can specifically stimulate and proliferate the human Vxcex32Vxcex42 type T cells thereby inducing and enhancing the antitumor effect thereof. As a result, they have found a pharmaceutically acceptable salt of 2-methyl-3-butenyl-1-pyrophosphoric acid, especially a sodium salt thereof as a novel organic pyrophosphoric acid compound. That is, they have found that, when lymphocytes in human blood such as peripheral blood or the lymph are treated by such an organic pyrophosphoric acid compound, Vxcex32Vxcex42 type T cells are specifically stimulated and proliferated whereby the antitumor effect thereof are induced and potentiated, and thus, the present invention has been completed.
Accordingly, the present invention relates to a pharmaceutically acceptable salt of 2-methyl-3-butenyl-1-pyrophosphoric acid which is a novel organic pyrophosphoric acid compound, especially a sodium salt thereof and to an agent for treating lymphocytes which comprises at least one selected from the group consisting of 2-methyl-3-butenyl-1-pyrophosphoric acid, a pharmaceutically acceptable salt thereof, especially a sodium salt thereof, and a hydrate thereof. Further, the present invention relates to Vxcex32Vxcex42 type T cells treated by the agent for treating lymphocytes, and a medicine which comprises the same.